Two Phase II studies demonstrated potential for pazopanib as a single agent treatment for early stage non-small cell lung cancer and advanced renal cell cancer:
LONDON and PHILADELPHIA, May 31 /PRNewswire-USNewswire/ -- GlaxoSmithKline today announced the results of two Phase II trials demonstrating the potential for pazopanib, an oral, investigational angiogenesis inhibitor, as a treatment for non-small cell lung cancer (NSCLC),(1) the most common form of lung cancer,(2) and renal cell carcinoma (RCC).(3) The data were presented at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Pazopanib is not approved in any market for any indication at this time.
Pazopanib targets vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR) and c-kit, key proteins that help with the growth of new blood vessels in the body.(4) This process, known as angiogenesis, plays a critical role in the growth and spread of tumors(5).
"These very promising results highlight the potential of pazopanib as a future treatment option across multiple forms of cancer," said Thierry Le Chevalier, M.D., Vice President, Oncology Medicine Development Center, GSK. "GSK is conducting a broad research program for pazopanib in a number of tumor types and this demonstrates our ongoing commitment to the development of innovative and effective treatments for patients with cancer."
Pazopanib and Non-Small Cell Lung Cancer: abstract 7557 (1)
DATA PRESENTATION: SUNDAY, JUNE 1, 2008, 11:00 AM - 12:00 PM (CDT)
This open-label, multi-center, Phase II study was designed to assess the activity of pazopanib when given to 35 treatment-naive patients with stage I-II NSCLC prior to surgery. Pre- and post- treatment high resolution computed tomography (HRCT) scans measuring tumor size showed that 30 patients (86 percent) had experienced a tumor volume reduction. Overall, patients experienced changes in tumor size ranging from a reduction of 86 percent to an increase of 17 percent.(1)
After an initial biopsy, 35 eligible patients had received 800 mg of pazopanib orally, once daily for two-six weeks, followed by a treatment free period of seven days prior to scheduled surgery to allow the administered drug to be eliminated from the body. The median duration of pazopanib therapy was 16 days.(1)
Grade 3 toxicities were seen in five patients while participating in study. These toxicities included elevated liver enzymes (2), hypertension (1), shortness of breath (1), pneumonia (1), urinary tract infection (1), reduced white blood cell count (1) potassium increase (1) and rash (1). One Grade 4 toxicity of a pulmonary embolus was seen in a patient in relation to surgery, 18 days after finishing pazopanib treatment. One patient discontinued treatment due to adverse events. Twelve patients required adjustment or initiation of antihypertensive medication during the study.(1)
Eight study centers participated in the trial in multiple countries including the US, Israel, and Spain. Based on these promising data, further studies with pazopanib in multiple stages of NSCLC are planned.
Pazopanib and Renal Cell Carcinoma: abstract 5046 (3)
DATA PRESENTATION: SUNDAY, JUNE 1, 2008, 11:00 AM - 12:00 PM (CDT)
This Phase II study was in 225 patients with advanced or metastatic RCC. The primary endpoint was to evaluate overall response rate according to RECIST criteria (Response Evaluation Criteria in Solid Tumors) - published guidelines that define when cancer patients improve. The study was originally designed as a randomized discontinuation trial. Patients received 800 mg of pazopanib once daily orally and response to treatment was measured at 12 weeks. Based on the interim analysis at week 12, 38 percent of patients had achieved a partial response (a decrease in the size of the tumor, or in the extent of cancer in response to treatment). This interim analysis prompted an Independent Data Monitoring Committee (IDMC) to recommend that patients with stable disease (cancer that is neither decreasing nor increasing in extent or severity) at week 12 should no longer be randomized to placebo. All patients randomized to placebo were therefore crossed over to pazopanib. The final results from the study were presented. Overall, the percentage of patients whose cancer responded to treatment was 35 percent and stable disease was achieved in 45 percent of patients at week 12. Responses were durable, with the median duration of response being 68 weeks. The estimated median progression-free survival (length of time during and after treatment in which a patient's disease does not get worse) was 11.9 months.
"In this clinical study, pazopanib demonstrated significant activity in terms of halting the progression of the disease in this patient population," said lead investigator Dr. Thomas Hutson, Baylor Sammons/Texas Oncology PA, Dallas, Texas. "These results support the ongoing Phase III investigation for pazopanib in renal cell cancer and bring us one step closer to an additional treatment option for patients."
The most frequent adverse events were diarrhea, hair color change, hypertension, nausea and fatigue. These positive findings support the ongoing Phase III development program in advanced or metastatic RCC; enrollment is complete in a Phase III trial and analysis is ongoing.(3)
About non-small cell lung cancer (NSCLC)
Lung cancer is the leading cause of cancer mortality, resulting in approximately 1.3 million deaths annually around the world.(6)
There are two main types of lung cancer - non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).(2) NSCLC is the most common form of lung cancer, accounting for about 87 percent of all lung cancers, and is associated with poor patient outcomes.(2) The majority of cases of NSCLC are diagnosed at an advanced stage and the five-year survival rate for all stages of disease combined is at maximum 15 percent. However, for localized cancers detected at an early stage, the five-year survival rate is 50 percent.(2)
Surgery, radiotherapy and chemotherapy are currently the standard treatments for lung cancer.(7) Surgery is usually recommended for early stage NSCLC, and if it can be done, it provides the best chance of a cure.(8)
About renal cell carcinoma (RCC)
The incidence of RCC is rising throughout the world(9) with 208,000 new cases diagnosed annually.(10) Surgery is the main treatment for most renal cell carcinomas.(1) The chances of surviving renal cell cancer without having surgery are small.(11) Approximately one-fourth of patients with renal cell carcinoma have metastasis at initial diagnosis, while 50 percent develop metastasis or local recurrence during follow-up after the treatment of the primary cancer.(12)
Although targeted therapies have improved the treatment of advanced or metastatic RCC, complete and durable responses are not achieved in the majority of patients,(13) and there remains a need for additional treatment options.
Pazopanib is an investigational, oral, once-daily angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit.(4) VEGF and PDGF are growth factors critical to the development and growth of blood vessels - a process known as angiogenesis. Angiogenesis plays a pivotal role in the growth and spread of several tumor types, with VEGF and PDGF overexpression linked to multiple cancers including cancers of the liver, lung, breast, kidney, bladder, ovaries, and colon.(14) By inhibiting VEGFR, PDGFR, and c-kit, pazopanib may stop or slow the rate of tumor growth and development. Pazopanib is currently being studied in a number of different tumor types; clinical trials are currently underway in RCC, breast cancer, ovarian cancer, soft tissue sarcoma, NSCLC, cervical cancer and other solid tumors. It is being evaluated as a monotherapy,(4) in combination with targeted therapies(15) and in combination with cytotoxic chemotherapy.(16) More than 1,400 patients have been treated to date in clinical trials. For further details please visit www.clinicaltrials.gov. Pazopanib is not approved for marketing by any regulatory body.
For additional information on GSK's Oncology portfolio or the data being presented at ASCO, including detailed product fact sheets and press releases, visit www.us.gsk.com/media. This information will be updated throughout the ASCO annual meeting. Please also see onsite contact information listed at the end of this release.
GSK in Oncology
GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK's revolutionary "bench to bedside" approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centers. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies. For more information about GSK Oncology, visit www.gskoncology.com
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Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK's operations are described under "Risk Factors" in the "Business Review" in the company's Annual Report on Form 20-F for 2007.
Notes to editors:
For on-site contact at ASCO May 30 - June 3, 2008:
U.S media only: Sarah Alspach - +1 215 287 6354
Global media: Gregory Clarke - +1 317 694 3545
European media: Sonja Luz - +44 7920 568 625
1. Altorki N et al. Preoperative treatment with pazopanib (GW786034) a multikinase angiogenesis inhibitor in early stage non-small cell lung cancer (NSCLC): a proof-of-concept phase II study. 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2008; poster presentation: abstract # 7557
2. American Cancer Society website, Cancer Statistics 2006 http://www.cancer.org/downloads/STT/CAFF2006PWSecured.pdf (Date of access April 2008)
3. Hutson TE, Davis ID, et al. Pazopanib (GW786034) is active in metastatic renal cell carcinoma (RCC): interim results of a phase II randomized discontinuation trial (RDT). 2008 ASCO Annual Meeting, Chicago, USA. Abstract number 5046
4. Sonpavde G. and Hutson T. Pazopanib: A Novel Multitargeted Tyrosine Kinase Inhibitor. Curr Oncol Rep. 2007; Mar;9(2):115-9
5. Jain RK. Antiangiogenic therapy for cancer: current and emerging concepts. Oncology. 2005 Apr;19(4 Suppl 3):7-16
6. World Health Organisation -- Cancer -- Fact Sheet nÂ° 297 (Feb 2006) http://www.who.int/mediacentre/factsheets/fs297/en/index.html (Date of access April 2008)
7. American Cancer Society website http://www.cancer.org/docroot/CRI/content/CRI_2_4_4x_Treatment_Options_15.asp?rnav=cri (Date of access April 2008)
8. American Cancer Society website http://www.cancer.org/docroot/CRI/content/CRI_2_4_4x_Surgery_15.asp?rnav=cri (Date of access April 2008)
9. Murai M. and Oya M. Renal cell carcinoma: etiology, incidence and epidemiology. Curr. Opin. Urol. 2004;14, 229-233.
10. Parkin M, Bray F et al. Global Cancer Statistics. CA Cancer J Clin. 2005;55:74-108
11. American Cancer Society. Detailed Guide: Kidney Cancer, Surgery. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Surgery_22.asp?sitearea= Accessed May 28, 2008.
12. Thyavihally B, et al. Management of renal cell carcinoma with solitary metastasis. World Journal of Surgical Oncology. 2005, 3:48.
13. Garcia JA, Rini B. Recent progress in the management of advanced renal cell carcinoma. CA Cancer J Clin. 2007 Mar-Apr;57(2):112-25.
14. Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist. 2004; 9 (Suppl 1): 2-10
15. Dejonge M, Savage S et al. A phase I, open-label study of the safety and pharmacokinetics (PK) of pazopanib (P) and lapatinib (L) administered concurrently. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 3088
16. Suttle B, Jones B, et al. Phase I study of the safety and pharmacokinetics (PK) of paclitaxel or paclitaxel with carboplatin administered in combination with pazopanib (GW786034). 43rd Annual Meeting of the American Society of Clinical Oncology (ASC)) 2007; poster presentation: abstract # 14118